Patent GB-595592-A (GB)
Title: Improvements in pharmaceutical preparations
IPC: A61K31/635
Filed: 1943-09-07
Abstract: Sulphanilamide derivatives for local application are made by interacting a sulphanilamide type compound capable of forming N-alkali salts or such salts with a vascoconstrictive amine or an acid addition salt thereof.  The expression vascoconstrictive amine means ephedrine and other alkylamines having a local vascoconstrictor action.  Those mentioned include ephedrine, amphetamine, epinephrine, kephrine, neo-synlphrine, propadrine and deoxyephedrine.  Compounds of the sulphanilamide type which are mentioned include sulphanilamide and chemotherapeutic derivatives and substitution products thereof such as sulphapyridine, sulphathiazole and the sulphadiazines.  In examples the following reactants are employed, and in some cases additional materials such as solvents stabilizers, gelling agents and other sulphanilamides are added: (1) sulphathiazole and ephedrine; (2) sodium sulphathiazole and neo-synephrine hydrochloride; (3), (5), (6), (7), (9) and (10) sodium sulphathiazole and desoxyephedrine hydrochloride; (4) sodium sulphathiazole and propadrine hydrochloride; (8) sodium sulphathiazole and ephedrine hydrochloride.ALSO:A pharmaceutical substance or composition for local application in the treatment of infections is obtained by admixing or interacting (i) a sulphanilamide-type compound capable of forming N-alkali salts, or (ii) such salts, with a vasoconstricting amine or an acid-addition salt thereof.  The expression vasoconstrictive amine denotes a  - hydroxy - b  - methylamino - propyl benzene and other phenyl-alkylamines having a local vasoconstrictor action. Compounds of the sulphanilamide type which are mentioned include sulphanilamide and chemotherapeutic derivatives and substitution products thereof such as sulphapyridine, sulphathiazole and the sulpha-diazines.  Amines mentioned include in addition to ephedrine b  - methylaminoethyl - benzene, a  - hydroxy - b  - methylaminoethyl - 3 : 4 - dihydroxy - benzene, methylaminoacetyl - 3 : 4 - dihydroxybenzene, a  - hydroxy - b  - methylaminoethyl - 3 - hydroxy - benzene, a  - hydroxy - b  - methylaminoethyl - 4 - hydroxybenzene, a  - hydroxy - b  - aminopropyl - benzene, a  - hydroxy - b  - aminopropyl - 3 : 4 - dihydroxybenzene, b -aminopropyl-4-hydroxy - benzene, b -methylaminopropyl-benzene.  Products embodying the sulphanilamide-type compound in excess (i.e. uncombined) are preferred and they are advantageously stabilized, when employed as aqueous solutions, by adding a water-soluble sulphite, especially an alkalimetal sulphite, e.g. sodium sulphite, and optionally there is incorporated in the solution thus stabilized a minute amount of a mono- or polyhydric alcohol, such as glycerol or isopropyl-, benzyl- or n- or secondary butyl alcohols.  Glycerol (up to about 10 per cent) may be added to the solution, and also phenolphthalein or other colouring agent, and traces of spearmint, wintergreen and/or peppermint oils, with a carrier of vanilla.  The reaction-products of the sulphanilamide-type compounds and vasoconstrictive amines, with or without the former in excess may be applied directly or in an aqueous medium preferably brought to pH 7.5-10 with sodium hydroxide, just prior to use.  The products of the invention may also be incorporated into an aqueous-jelly vehicle.  In examples: (1) sulphathiazole is boiled with aqueous ephedrine to obtain ephedronium sulphathiazole, which may be employed per se as a pharmaceutical substance; (2) sodium sulphathiazole is dissolved in distilled water containing glycerol and sodium sulphite, followed by neo-synephrine hydrochloride, and an ethanolic solution of colouring and flavouring substances and the pH of the mixture may be adjusted with dilute hydrochloric acid; (3) sodium sulphathiazole and desoxyephedrine hydrochloride are admixed dry and pelletted; (4) sodium sulphathiazole, a  - hydroxy - b  - aminopropyl benzene hydrochloride (propadrine hydrochloride), sodium sulphite, glycerol and colouring and flavouring substances in ethanol are made into an aqueous mixture as in (2); (5) the propadrine hydrochloride of example (4) is replaced by desoxyephedrine hydrochloride; (6) an aqueous solution containing sodium sulphathiazole, sodium sulphite, glycerine and desoxyephedrine hydrochloride is added to an aqueous solution of methyl cellulose to obtain a gelatinous mass; (7) as in example (6) with the addition of sodium sulphanilamide; (8) ephedrine hydrochloride is added to an aqueous solution of sodium sulphathiazole; (9) desoxyephedrine hydrochloride is added to an aqueous solution of sodium sulphathiazole and the product extracted with alcohol and precipitated with ether; (10) as in example (9), but using propadrine hydrochloride.